Open AccessS100B Serves as a Ca2+Sensor for ROS-GC1 Guanylate Cyclase in Cones but not in Rods of the Murine Retina
Author(s) -
Xiaohong Wen,
Teresa Duda,
Alexandre Pertzev,
V. Venkataraman,
Clint L. Makino,
Rameshwar K. Sharma
Publication year - 2012
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000338496
Subject(s) - visual phototransduction , microbiology and biotechnology , gucy2d , retina , second messenger system , biophysics , transducin , signal transduction , transduction (biophysics) , biology , calcium signaling , neurotransmission , guanylate cyclase , chemistry , guanylate cyclase 2c , neuroscience , biochemistry , receptor , g protein
Rod outer segment membrane guanylate cyclase (ROS-GC1) is a bimodal Ca(2+) signal transduction switch. Lowering [Ca(2+)](i) from 200 to 20 nM progressively turns it "ON" as does raising [Ca(2+)](i) from 500 to 5000 nM. The mode operating at lower [Ca(2+)](i) plays a vital role in phototransduction in both rods and cones. The physiological function of the mode operating at elevated [Ca(2+)](i) is not known. Through comprehensive studies on mice involving gene deletions, biochemistry, immunohistochemistry, electroretinograms and single cell recordings, the present study demonstrates that the Ca(2+)-sensor S100B coexists with and is physiologically linked to ROS-GC1 in cones but not in rods. It up-regulates ROS-GC1 activity with a K(1/2) for Ca(2+) greater than 500 nM and modulates the transmission of neural signals to cone ON-bipolar cells. Furthermore, a possibility is raised that under pathological conditions where [Ca(2+)](i) levels rise to and perhaps even enter the micromolar range, the S100B signaling switch will be turned "ON" causing an explosive production of CNG channel opening and further rise in [Ca(2+)](i) in cone outer segments. The findings define a new cone-specific Ca(2+)-dependent feature of photoreceptors and expand our understanding of the operational principles of phototransduction machinery.